IgE-Mediated Reactions and Anaphylactic Shock
IgE-mediated reactions can cause anaphylactic shock, but not all anaphylactic shock is IgE-mediated—delayed hypersensitivity reactions are typically caused by T-cell mechanisms (Type IV), not immunoglobulins. 1, 2
Understanding IgE-Mediated Anaphylaxis
IgE-mediated reactions represent one mechanism of anaphylactic shock, occurring when allergen exposure triggers mast cell and basophil activation through IgE receptor cross-linking. 1 This process leads to:
- Rapid release of histamine within 5 minutes of mast cell activation, remaining elevated for 15-60 minutes 2
- Vasodilation, increased vascular permeability, and smooth muscle contraction 2
- Clinical manifestations including urticaria, angioedema, bronchospasm, hypotension, and cardiovascular collapse 2, 3
The European Academy of Allergy and Clinical Immunology (EAACI) clarifies that "allergic anaphylaxis" should only be used when the reaction is mediated by an immunological mechanism such as IgE, IgG, or complement activation. 1 An IgE-mediated anaphylactic reaction, such as to amoxicillin, is specifically termed "IgE-mediated allergic anaphylaxis." 1
Non-IgE Mechanisms Can Also Cause Anaphylactic Shock
Critically, anaphylactic shock can occur through non-IgE pathways that produce clinically identical presentations. 1, 4 These include:
- IgG antibody-mediated reactions that activate neutrophils 4, 5
- Anaphylatoxin activation (complement-mediated) 1
- Direct mast cell activation through G-coupled receptors 4
- Inflammatory mediators like bradykinin or prostaglandins causing direct vasodilation 4
The term "anaphylactoid" was previously used for non-IgE-mediated reactions but is no longer recommended by EAACI, though American guidelines still use this terminology. 1
Delayed Reactions: T-Cell Mediated, Not Immunoglobulin-Driven
Delayed hypersensitivity reactions occurring more than 1 hour after drug administration are typically T-cell-dependent (Type IV) mechanisms, not mediated by any immunoglobulin class. 2, 6
Key characteristics of delayed reactions:
- Onset timing: More than 1 hour after administration, commonly developing after many days (typically early in the second week) 2
- Mechanism: T-cell mediated (Type IV hypersensitivity), not antibody-mediated 2, 6
- Clinical presentations: Maculopapular exanthema, DRESS syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis 2
- Management: Immediate drug discontinuation, topical corticosteroids, oral antihistamines for mild cases; systemic corticosteroids and specialized care for severe reactions 2
Clinical Distinction: Immediate vs. Delayed
The critical temporal distinction is that immediate reactions (within 1 hour) are often—but not exclusively—IgE-mediated, while delayed reactions (>1 hour, often days later) are T-cell mediated. 2, 6
For immediate reactions:
- Serum tryptase elevation (peaks within 1-2 hours) confirms mast cell activation 2
- Plasma histamine and urinary histamine metabolites aid diagnosis 2
- Epinephrine 0.01 mg/kg intramuscularly is first-line treatment 2, 3, 7
Common Pitfalls
Do not assume all anaphylactic reactions are IgE-mediated—this misconception can lead to inappropriate testing and counseling. 1, 4 Radiographic contrast material reactions, for example, are clinically identical to IgE-mediated anaphylaxis but typically occur through non-immunologic mechanisms. 1
Delayed reactions are not caused by IgE, IgG, or any other immunoglobulin—they are T-cell mediated. 2, 6 Testing for drug-specific IgE antibodies will be negative in true delayed hypersensitivity reactions.
Beta-blockers and ACE inhibitors increase the risk of severe anaphylactic reactions and reduce epinephrine effectiveness, regardless of the underlying mechanism. 1, 2